Formulations and methods for treating diarrhea

Abstract

Amino acid formulations useful for treating diarrhea in a subject in need thereof are described herein. Such amino acid formulations and methods comprising administering same to a subject are useful for treating diarrhea, particularly diarrhea caused by or associated with bacterial infections wherein secretagogue-stimulated anion secretion from the intestinal crypt contributes to at least one symptom of diarrhea in the subject. Use of these amino acid formulations for the treatment of diarrhea in general or diarrhea associated with secretagogue-stimulated anion secretion from the intestinal crypt are encompassed herein, as are their use in the preparation of a medicament for the treatment of diarrhea in general or diarrhea associated with secretagogue-stimulated anion secretion from the intestinal crypt.

1 . A formulation for use in treating diarrhea in a subject in need thereof, wherein the formulation comprises a therapeutically effective combination of free amino acids:
 the free amino acids consisting essentially of or consisting of a therapeutically effective amount of free amino acids of proline and aspartic acid; and   a therapeutically effective amount of at least one of free amino acids of serine, threonine, glycine, alanine, arginine, or tyrosine, or any combination thereof; and   optionally, free amino acids of asparagine; or   optionally,
 monosaccharide glucose, 
 at least one glucose-containing disaccharide, or 
 any combination thereof, 
   wherein the total concentration of the monosaccharide glucose, the at least one glucose-containing disaccharide, or any combination thereof is equal to or less than 90 mM; or   optionally, at least one pharmaceutically acceptable carrier, buffer, electrolyte, adjuvant, excipient, or water, or any combination thereof; or   any combination thereof; and   wherein the therapeutically effective combination of free amino acids is sufficient to reduce at least one symptom associated with the diarrhea in the subject.   
     
     
         2 . The formulation according to  claim 1 , wherein the concentration of proline ranges from 0.5 mM to 13 mM; wherein the concentration of aspartic acid ranges from 1 mM to 18 mM; wherein when serine is present, the concentration of serine ranges from 1.5 mM to 12 mM; wherein when threonine is present, the concentration of threonine ranges from 0.5 mM to 12 mM; wherein when glycine is present, the concentration of glycine ranges from 0.4 mM to 12 mM; wherein when alanine is present, the concentration of alanine ranges from 1.5 mM to 12 mM; wherein when arginine is present, the concentration of arginine ranges from 0.8 mM to 12 mM; wherein when tyrosine is present, the concentration of tyrosine ranges from 0.1 mM to 1.2 mM; wherein when asparagine is present, the concentration of asparagine ranges from 2 mM to 12 mM. 
     
     
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         11 . The formulation according to  claim 1 , wherein the therapeutically effective combination of free amino acids consists essentially of or consists of a therapeutically effective amount of free amino acids of proline, aspartic acid, serine, threonine, glycine, alanine, arginine, and tyrosine. 
     
     
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         16 . The formulation according to  claim 1 , wherein the therapeutically effective combination of free amino acids consists essentially of or consists of a therapeutically effective amount of free amino acids of proline, aspartic acid, serine, threonine, alanine, arginine, and tyrosine. 
     
     
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         19 . The formulation according to  claim 1 , wherein the formulation further comprises a pharmaceutically acceptable carrier, buffer, electrolyte, adjuvant, excipient, or water. 
     
     
         20 . The formulation according to  claim 1 , wherein the formulation is sterile. 
     
     
         21 . The formulation according to  claim 1 , wherein at least one of the free amino acids or each of the free amino acids comprises L-amino acids. 
     
     
         22 . The formulation according to  claim 1 , wherein the formulation does not comprise monosaccharide glucose, at least one glucose-containing disaccharide, or any combination thereof. 
     
     
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         24 . The formulation according to  claim 1 , wherein the formulation is formulated for administration by a parenteral, pulmonary, inhalation, intranasal, enteral, intravenous, anal, or sublingual route. 
     
     
         25 . The formulation according to  claim 1 , wherein the formulation is formulated for oral administration. 
     
     
         26 . The formulation according to  claim 1 , wherein the subject is a mammal. 
     
     
         27 . The formulation according to  claim 1 , wherein the mammal is a human, cat, dog, pig, horse, cow, sheep, or goat. 
     
     
         28 . The formulation according to  claim 1 , wherein the mammal is a human. 
     
     
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         30 . The formulation according to  claim 1 , wherein the diarrhea is associated with an infection by bacteria that produce a secretagogue in the subject. 
     
     
         31 . The formulation according to  claim 1 , wherein the bacteria comprise at least one of an enterotoxin-producing bacteria or an enterotoxigenic bacteria, or any combination thereof. 
     
     
         32 . The formulation according to  claim 1 , wherein the enterotoxin-producing bacteria comprises  Vibrio cholerae, Staphylococcus aureus, Bacillus cereus, Clostridium difficile, Clostridium perfringens, Staphylococcus aureus, Yersinia enterocolitica, Shigella dysenteriae , or an enterotoxigenic  Escherichia coli , or any combination thereof. 
     
     
         33 . The formulation according to  claim 1 , wherein the at least one symptom associated with diarrhea comprises at least one of loose, watery stools; abdominal cramps; abdominal pain; fever; blood in the stool; mucus in the stool; bloating; or nausea; or any combination thereof. 
     
     
         34 . The formulation according to  claim 1 , wherein reducing the at least one symptom associated with diarrhea comprises a reduction in at least one of volume of loose, watery stools per day; or frequency of loose, watery stools per day; or any combination thereof. 
     
     
         35 . The formulation according to  claim 1 , wherein the formulation is formulated for use as a medicament for the treatment of diarrhea. 
     
     
         36 . A method for treating diarrhea in a subject in need thereof, the method comprising:
 administering to the subject in need thereof the formulation according to  claim 1 ,   wherein the administering reduces at least one symptom associated with diarrhea in the subject.   
     
     
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